The
publicly funded International Human Genome Project (HGP)
consortium using the "hierarchical shotgun
approach," and Dr. Craig Venter's Celera Corporation using
the "whole-genome shotgun approach"
(WGS)
achieved the nearly
complete joining of all the sequence fragments of the human genome into
one. The tentative identification of some 40,000 genes was announced in
the New York Times of 11th February 2001:

"In
principle," the consortium's biologists concluded in their
report, "the string of genetic bits holds long-sought
secrets of human development, physiology and medicine. In
practice, our
ability to transform such knowledge into understanding remains
woefully inadequate."

Dr. Venter said simply that the effort to sequence and interpret
the human genome had been "mentally exhausting, in part
because we are not mentally equipped to absorb all this."
... "We feel like midgets describing the universe and we
can't comprehend it all," he added.

It is for the reader to
ponder Venter's mental exhaustion. His organizational and marketing
skill are hardly to be doubted. But if those seeking to
understand the genome through bioinformatic and evolutionary analysis
had had just one fraction of a percent of the funds available to the
Consortium and Celera, they might have already achieved the
transformation of mere data (let us not dignify it as
"knowledge") into understanding?
Sydney Brenner pointed out:

"Sequencing large
genomes has nothing to do with intellectual endeavour. The
creative work was done earlier by Fred Sanger and by others who
improved the technology. The rest is about two things: money and
management. As the various projects developed, their demand for
money increased. The nematode sequencing project quickly consumed
most of the funds available for genome work at a time when money
was short."

(2002; Nature416, 794-5)

Along similar lines
Margaret Somerville commented:

"Conditions that are
attached to government funding can affect the purposes and values
upheld, especially when those conditions require academic-industrial
partnerships for research to be eligible for funding, as in the case
of the Canadian government's C $300 ... million investment in a
series of genomics research centres (Genome Canada). Structuring
funding in this way leaves out the funding of research that will not
result in marketable products, and excludes those researchers who
undertake it."

(2002; Nature Reviews1, 316-320)

And let us not pretend that
we actually needed the sequence of the entire human genome in order to
complete our understanding. Just as one does not need access to an
entire dictionary if one wants to understand how a dictionary works, so
one does not need access to an entire genome to find out how genomes
work. And for most of us an entire dictionary is redundant. Our needs
are highly selective. Few of us want to look up the word "and."
Many might want to look up the word "esoteric."

Similarly, techniques developed in the early 1980s (e.g. Forsdyke 1985)
allow us to selectively access genes likely to be of importance
(Click Here). We now
have an excess of human genomic sequences, not because they might reveal
"long-sought
secrets of human development, physiology and medicine,"but because the project is highly marketable, and because of
patent possibilities. Those who really want to understand the human
genome know that it is far more important to sequence comparable segments
of non-human genomes. For more on this please go to my bioinformatic
web-page (Click Here),
and see below.

Donald Forsdyke

Did
Celera invent the internet?

The Lancet357,
1203 (#9263; 14th April 2001)

Sir--The overtaking of publicly funded research teams by Celera Genomics
in its completion of the sequencing of the human genome, to which you
refer in your
Jan 13 editorial,1 smacks somewhat of the Sputnik
episode.

The United States of Soviet Russia scaled up
the payload of their rocket and put a man into space before the USA, but
did not make parallel progress in the other technologies required to
capitalise on this advance. Craig Venter, the chief executive officer of
Celera, has stated that understanding the genome may help resolve
previously unanswerable questions.2 But Celera has merely
made available the full text of the genome a little sooner than we might
otherwise have had it. Those of us working to understand the genome3
no more need the full text of the genome than you would need the full
text of a dictionary if you were trying to understand how a dictionary
works.

You state that, courtesy of Celera, the
entire sequence will be available free of charge;1 a Celera
spokesman has declared that academic users will have to pay US$7000 per
year.4 That the beneficence, and perhaps the integrity, of
Celera might not be relied on, was suggested by a full-page colour
advertisement in Canada's leading newspaper. This advertisement, in
large capital letters, declared "The
skeptics were right when they said Craig Venter would never crack the
human genetic code on schedule. He was two years early".

We smiled when Al Gore told us he had invented the
Internet, and he quickly apologised and expressed remorse. Yet, here is
the chief executive officer of Celera claiming to have cracked the
genetic code--a feat achieved in the 1960s, and for which Nobel prizes
were awarded in 1968. My protest in a letter to the newspaper on Jan 15,5
which was forwarded to Venter's corporate sponsors, was answered by
repeats of the advertisement on Jan 16, 22, and 25.

For more on Marshall Nirenberg, who was one of those who received the
Nobel Prize in 1968 for cracking the genetic code (Click
Here)

Let the
Cobbler Stick to his Last

The
human sequence was deposited in various electronic databases.
However, the sequencers, having delivered up the human genome, had to
report the fact in the scientific literature. Their task was to describe
any novel aspects of the methodology, compare the two sequence
approaches, and outline the general features of the
genome. That was all. To his credit Venter expressed some diffidence
(see above). However, the temptation to go beyond their brief
was too great. The speculations of the genome amateurs were soundly quashed by
the great "genomographer" of our times, Giorgio Bernardi,
in a two part article in Gene (2001;
276, 3-13) euphemistically entitled
"misunderstandings." (not
reproduced here)

Did Celera independently
sequence the human genome?

To
this question the answer seems to be negative. In March 2002 (Proc.
Natl. Acad. Sci. USA 99,
3712-16) some
members of the publicly funded consortium who had used the hierarchical
shotgun approach pointed out that:

"In principle, the availability of two
papers on the human genome has much potential scientific
benefit. In addition to the comparison of two independently
derived genome sequences, it should allow methodological analysis
of the sequencing strategies used for insights concerning the
design of future genome-sequencing efforts."

The authors concluded
that the Celera approach:

"Primarily depended on the HGP's
sequence-tagged site maps, BAC maps, and clone-based sequences.
Our analysis indicates that the Celera paper provides neither a
meaningful test of the WGS approach nor an independent sequence
of the human genome."

The Celera group
considered that "this conclusion is based on incorrect assumptions
and flawed reasoning." (2002; PNAS99, 4145-46.